Bradykinin is a Mediator, but Unlikely a Trigger, of Antiarrhythmic Effects of Ischemic Preconditioning

• Published in: Journal of cardiovascular electrophysiology 2007-01, Vol.18 (1), p.93-99
• Main Authors: DRIAMOV, SERGEY V., BELLAHCENE, MOHAMED, BUTZ, SILVIA, BUSER, PETER T., ZAUGG, CHRISTIAN E.
• Format: Article
• Language: English
• Subjects: Animals; arrhythmias; bradykinin; Bradykinin - analogs & derivatives; Bradykinin - drug effects; Bradykinin - metabolism; Bradykinin - pharmacology; Bradykinin Receptor Antagonists; Disease Models, Animal; Disease Progression; Electrocardiography; Heart Rate - physiology; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Heart Ventricles - physiopathology; Ischemic Preconditioning, Myocardial - methods; Male; Pilot Projects; preconditioning; Prognosis; protection; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular - etiology; Tachycardia, Ventricular - metabolism; Tachycardia, Ventricular - prevention & control; Ventricular Fibrillation - etiology; Ventricular Fibrillation - metabolism; Ventricular Fibrillation - prevention & control
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1111/j.1540-8167.2006.00688.x

Objective: Brief reversible ischemic episodes (ischemic preconditioning, IPC) protect the heart against arrhythmias during a subsequent prolonged low‐flow ischemia. We have recently shown that this protection involves release of bradykinin, activation of bradykinin B2 receptors followed by opening of sarcolemmal, but not mitochondrial ATP‐sensitive K+ channels. The goal of this study was to clarify a trigger and/or mediator role of bradykinin in the antiarrhythmic effects of IPC during low‐flow ischemia. Methods: Isolated perfused rat hearts underwent 60 minutes of low‐flow ischemia induced by reducing perfusion pressure followed by 60 minutes of reperfusion. Preconditioning was induced by 2 × 5 minutes episodes of zero‐flow ischemia. In yet other groups, preconditioned or nonpreconditioned hearts were treated either with bradykinin (10 nmol/L) or with HOE 140 (bradykinin B2 receptor antagonist, 100 nmol/L). Results: IPC reduced the number of ventricular premature beats, as well as the incidence of ventricular tachycardia and of ventricular fibrillation during low‐flow ischemia. In addition, this protection was abolished by HOE 140 given during low‐flow ischemia. Pharmacological preconditioning using short bradykinin perfusion instead of IPC did not show antiarrhythmic effects. However, bradykinin administered during low‐flow ischemia and reperfusion reduced the number of ventricular premature beats and the incidence of ventricular tachycardia and of ventricular fibrillation during low‐flow ischemia. Conclusion: Bradykinin is a mediator, but unlikely a trigger, of antiarrhythmic effects of IPC during low‐flow ischemia.